Abstract
Holt-Oram syndrome is a developmental disorder affecting the heart and upper limb, the gene for which was mapped to chromosome 12 two years ago. We have now identified a gene for this disorder (HOS1). The gene (TBX5) is a member of the Brachyury (T) family corresponding to the mouse Tbx5 gene. We have identified six mutations, three in HOS families and three in sporadic HOS cases. Each of the mutations introduces a premature stop codon in the TBX5 gene product. Tissue in situ hybridization studies on human embryos from days 26 to 52 of gestation reveal expression of TBX5 in heart and limb, consistent with a role in human embryonic development.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Abnormalities, Multiple / genetics*
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Amino Acid Sequence
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Animals
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Arm / abnormalities*
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Base Sequence
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Cell Line
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Chromosomes, Artificial, Yeast
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Chromosomes, Human, Pair 12
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DNA
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DNA-Binding Proteins / genetics
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Embryo, Mammalian / metabolism
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Female
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Fetal Proteins / genetics
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Gene Expression
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Heart Defects, Congenital / genetics*
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Humans
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Male
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Mice
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Molecular Sequence Data
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Multigene Family
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Pedigree
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RNA, Messenger / genetics
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Sequence Homology, Amino Acid
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Syndrome
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T-Box Domain Proteins*
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Transcription Factors / genetics*
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Transcription, Genetic
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Translocation, Genetic
Substances
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DNA-Binding Proteins
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Fetal Proteins
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RNA, Messenger
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T-Box Domain Proteins
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T-box transcription factor 5
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Transcription Factors
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DNA
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Brachyury protein